Function and regulation of the WASH complex in the endocytic cycle

[摘要] The WASH complex is highly conserved and consists of the actin nucleation promoter, WASH, and several regulatory subunits; Strumpellin, SWIP, ccdc53 and FAM21.Previously, it has been shown that WASH directs construction of actin coats on lysosomes.This actin coat is required for removal of V-ATPase complexes from lysosomal membranes, allowing neutralization and maturation to post-lysosomes.WASH null cells are blocked at the acidic lysosome stage and are thus unable to perform exocytosis.We now show that FAM21 acts at a different step in the same pathway. FAM21 nulls are still blocked in exocytosis, but the remaining complex is functional in removal of V-ATPase, allowing progression to post-lysosome.We hypothesize that the role of FAM21 is to release the WASH complex from post-lysosome membranes in order to allow recycling back to newly formed acidic lysosomes.We have also shown that capping protein interacts with the WASH complex through FAM21, and this interaction is essential for progression to exocytosis, likely contributing to the mechanism by which FAM21 regulates and releases the WASH complex from post-lysosomal membranes.

[发布机构] University:University of Glasgow;Department:Institute of Cancer Sciences

[关键词] WASH complex, endocytosis, exocytosis, actin, vesicle, lysosome